cAMP-induced Interleukin-10 promoter activation depends on CCAAT/enhancer-binding protein expression and monocytic differentiation

J Biol Chem. 2003 Feb 21;278(8):5597-604. doi: 10.1074/jbc.M207448200. Epub 2002 Dec 18.


The molecular mechanisms underlying the regulation of interleukin (IL)-10 transcription in monocytic cells by various stimuli during inflammation and the stress reaction are not fully understood. Recently, we provided evidence that stress-induced IL-10 promoter activation in monocytic cells is mediated by catecholamines via a cAMP-dependent signaling pathway including CREB/ATF (cAMP-responsive element binding protein/activating transcription factor) binding to two CRE motifs. However, the mutation of these sites diminished cAMP responsiveness by only 50%, suggesting a role for additional transcription factors and elements in the cAMP-dependent regulation of the human IL-10 promoter. Here, we analyze the functional role of one such factor, C/EBP, in two cell lines of myelomonocytic origin, THP-1 and HL-60, which are known to differ in their differentiation status and C/EBP protein content. We show that the level of basal as well as cAMP-stimulated IL-10 transcription depends on the expression of C/EBP alpha and beta and their binding to three motifs in the promoter/enhancer region. The C/EBP5 motif, which is located between the TATA-box and the translation start point, is essential for the C/EBP-mediated constitutive and most of the cAMP-stimulated expression as its mutation nearly abolished IL-10 promoter activity. Our results suggest a dominant role of C/EBP transcription factors relative to CREB/ATF in tissue-specific and differentiation-dependent IL-10 transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bucladesine / pharmacology*
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Cell Differentiation
  • Codon, Initiator
  • Cyclic AMP / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • HL-60 Cells
  • Humans
  • Interleukin-10 / genetics*
  • Mice
  • Molecular Sequence Data
  • Monocytes / cytology*
  • Monocytes / immunology
  • Muridae
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic*
  • Protein Biosynthesis
  • Recombinant Proteins / immunology
  • TATA Box
  • Transcription, Genetic / immunology*
  • Transfection


  • CCAAT-Enhancer-Binding Proteins
  • Codon, Initiator
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Interleukin-10
  • Bucladesine
  • Cyclic AMP